Microdeletion Syndromes Detected by FISH – 73 Positive from 374 Cases

Fluorescence in situ hybridization (FISH) has facilitated the detection of microdeletions seen in PraderWilli/Angelman (PW/AS), Williams and DiGeorge syndromes. Out of 374 suspected cases tested at Jaslok Hospital in the past 5 years, 73 were positive, including 29 cases of Angelman, 16 of Prader-Willi, 24 of Williams and 4 of DiGeorge syndrome. Male preponderance was seen, mainly in Williams syndrome. The mechanisms causing PraderWilli and Angelman syndrome include microdeletions, intragenic mutations, uniparental disomy and imprinting defects, though FISH can only detect microdeletions. Metaphase FISH helped to detect 1 case each with deletion of the control (PML) signal and duplication of the critical PW/AS region, which are associated with autism. One suspected case of Prader-Willi syndrome had a Robertsonian translocation t(14;15)(q10;q10) which led to a deletion of a major part of the SNRPN region in 10% cells, resulting in low-grade mosaicism. Another FISH-positive case was due to a reciprocal translocation t(2;15)(q37;q11), where loss of critical genes at the breakpoint on chromosome 15 caused the Prader-Willi phenotype. FISH in a child with an Angelman phenotype showed no microdeletion, though Trisomy 15 was seen in 1 metaphase suggesting uniparental disomy due to trisomy rescue. A known polymorphism in the form of an additional tiny green signal on chromosome 14 was observed in 17 of 284 (6%) cases studied for Prader-Willi/Angelman syndrome. Another inherited polymorphism was seen in 5 cases, where one control signal was very small. Prenatal diagnosis was carried out with normal results, in 12 women with a previously affected child.